|NHGRI Expands Effort to Revolutionize
Grants Awarded to Develop Faster, Cheaper DNA Sequencing
Bethesda, Maryland — The National Human
Genome Research Institute (NHGRI), part of the National
Institutes of Health (NIH), today announced it has awarded
grants totaling more than $32 million to advance the
development of innovative sequencing technologies intended
to reduce the cost of DNA sequencing and expand the
use of genomics in biomedical research and health care.
“The efforts are aimed at speeding the rate at which
the next generation of sequencing technologies become
available in the scientific lab and the medical clinic,” said
NHGRI Director Francis S. Collins, M.D., Ph.D. “Not
only will these technologies substantially reduce the
cost of sequencing a genome, but they will provide a
quantum leap in the scope and scale of research aimed
at uncovering the genomic contributions to common diseases,
such as cancer, heart disease and diabetes.”
Over the past decade, DNA sequencing costs have fallen
more than 50-fold, fueled in large part by tools, technologies
and process improvements developed as part of the successful
effort to sequence the human genome. However, it still
costs about $10 million to sequence 3 billion base pairs — the
amount of DNA found in the genomes of humans and other
NHGRI’s near-term goal is to lower the cost of sequencing
a mammalian-sized genome to $100,000, which would enable
researchers to sequence the genomes of hundreds or even
thousands of people as part of studies to identify genes
that contribute to common, complex diseases. Ultimately,
NHGRI’s vision is to cut the cost of whole-genome sequencing
to $1,000 or less, which would enable the sequencing
of individual genomes as part of routine medical care.
The ability to sequence an individual genome cost-effectively
could enable health care professionals to tailor diagnosis,
treatment and prevention to each person’s unique genetic
The new grants balance NHGRI’s sequencing research
portfolio by supporting more investigators working on
technologies that would make it feasible to sequence
a genome for $1,000. The majority of researchers who
received NHGRI’s initial sequencing technology grants,
issued in October 2004, are aimed at sequencing a genome
for $100,000. Both approaches have many complementary
elements that integrate biochemistry, chemistry and
physics with engineering to enhance the whole effort
to develop the next generation of DNA sequencing and
“It is very important that we encourage and support
the variety of sequencing technology projects that hold
the most promise for revolutionizing genome sequencing.
Each research team brings a unique set of skills and
expertise to solving difficult scientific and engineering
problems,” said Jeffery Schloss, Ph.D., NHGRI’s program
director for technology development. “The different
approaches will likely yield several successful and
complementary technologies. It is going to be interesting
to see how each technology progresses and which of them
can ultimately be used by the average researcher or
“$1,000 Genome” Grants
NHGRI’s “Revolutionary Genome Sequencing Technologies” grants
have as their goal the development of breakthrough technologies
that will enable a human-sized genome to be sequenced
for $1,000 or less. Grant recipients and their approximate
total funding are:
Richard B. Fair, Ph.D., Duke University, Durham, N.C.
$510,000 (2 years)
“Droplet-Based Digital Microfluidic Genome Sequencing”
The near-term goal of this group is to demonstrate
how existing droplet-based microfluidic electro-wetting
technology can be modified to perform sequencing by
synthesis reaction chemistry. This method allows for
smaller volumes of materials to be used as well as the
decoupling of synthesis and detection steps, resulting
in more efficient automation.
M. Reza Ghadiri, Ph.D., The Scripps Research Institute,
La Jolla, Calif. and
Hagan P. Bayley, Ph.D., Oxford University, UK.
$4.2 million (5 years)
“Single-Molecule DNA Sequencing with Engineered Nanopores”
This project is a collaborative effort between two
laboratories that have experience in nanopore research,
protein engineering and molecular recognition. The group
will engineer a device with the ability to recognize
a nucleotide on the basis of changes in electrical current,
as it passes through a membrane with tiny channels known
Jene A. Golovchencko, Ph.D., Harvard University, Cambridge,
$5.2 million (3 years)
“Electronic Sequencing in Nanopores”
The objective of this project is to develop a general
utility instrument to provide inexpensive sequencing
that can also be used for projects to recognize genome
variation. The group will design novel nanopores articulated
with probes to sequentially, and directly, identify
nucleotides in very long fragments of genomic DNA based
on their unique electronic signals.
Susan H. Hardin, Ph.D., VisiGen Biotechnologies, Houston.
$4.2 million (3 years)
“Real-Time DNA Sequencing”
This group is developing a sequencing system in which
polymerase (an enzyme used to synthesize DNA molecules)
and nucleotides act together as direct molecular sensors
of DNA base identity. The key to the system is the interaction
between a fluorescent polymerase and the nucleotide,
which emits a signature detectable in real-time.
Xiaohua Huang, Ph.D., University of California, San
Diego, La Jolla.
$750,000 (3 years)
“Massively Parallel Cloning and Sequencing of DNA”
The goal of this project is to develop two innovative
technologies: massively parallel, whole-genome amplification
and DNA sequencing by denaturation. The resulting system
amplifies DNA directly on a microchip, enabling the
process of sequencing to be done on a single miniaturized
Jingyue Ju, Ph.D., Columbia University, New York.
$970,000 (3 years)
“Modulating Nucleotide Size in DNA for Detection by Nanopore”
This group will design and synthesize modified nucleotides
of different sizes, which can be incorporated into DNA.
When passed through nanopores, the differences between
these modified nucleotides will be easier to detect,
producing clean sequencing data.
Bhubaneswar (Bud) Mishra, Ph.D., New York University,
$585,000 (2 years)
“Haplotype Sequencing Via Single Molecule Hybridization”
Investigators from this group will hybridize short
DNA probes to genomic DNA fragments to determine sequence
information. In addition, they will use optical mapping
to create restriction maps to help assemble the genome
once it is sequenced. The group will then demonstrate
how to combine the sequence and maps into distinct haplotype
Gregory L. Timp, Ph.D., University of Illinois, Urbana-Champaign.
$2.1 million (3 years)
“Sequencing a DNA Molecule Using a Synthetic Nanopore”
This group will explore the feasibility of sequencing
a DNA molecule using a type of silicon integrated circuit.
The circuit incorporates a nanopore mechanism with a
molecular trap that forces the DNA molecule to oscillate
back and forth between electrodes, measuring the electrical
signal associated with each specific base.
Stephen W. Turner, Ph.D., Nanofluidics, Menlo Park,
$6.6 million (3 years)
“Real-Time Multiplex Single-Molecule DNA Sequencing”
This group will leverage their “zero-mode waveguide” technology
to detect single nucleotides in real-time, as they are
incorporated by a DNA polymerase into a growing DNA
molecule. The ultimate goal is to create a real-time,
multiplex single-molecule DNA sequencing system that
produces sequence reads containing hundreds of thousands
“$100,000 Genome” Grants
NHGRI’s “Near-Term Development for Genome Sequencing” grants
will support research aimed at sequencing a human-sized
genome at 100 times lower cost than is possible today.
There is strong potential that, five years from now,
some of these technologies will be at or near commercial
availability. Grant recipients and their approximate
total funding are:
Gina L. Costa, Ph.D., Agencourt Personal Genomics,
$1.2 million (2 years)
“Bead-Based Polony Sequencing”
Supplemental funding is expected to accelerate commercialization
of this technology that will use oligonucleotide ligation
to read DNA sequence, using bead-based, polymerase colony
(polony) sequencing technology.
Vera B. Gorfinkel, Ph.D., The State University of
New York (SUNY),
Stony Brook, N.Y.
$1.5 million (2 years)
“Ultra High Throughput DNA Sequencing System Based on Two-Dimensional
Monolith Multi-Capillary Arrays and Nanoliter Reaction Volume”
This group will develop and implement an efficient
method capable of sequencing mammalian size genomes
by amplifying single template molecules, and subjecting
the product to Sanger sequencing and a highly parallel,
capillary electrophoresis separation system.
Greg Kellogg, Ph.D., Network Biosystems, Woburn, Mass.
$4.5 million (3 years)
“$100,000 Genome Using Integrated Microfluidic Capillary Electrophoresis”
This group will work to improve performance of Sanger
sequencing and PCR as compared to that attainable using
capillary electrophoresis systems. To do so, it will
miniaturize and integrate current sequencing technologies,
building on its microfluidics platform.
For more details about the NHGRI sequencing technology
development grants, go to: http://www.genome.gov/15015202.
NHGRI is one of 27 institutes and centers at NIH, an
agency of the Department of Health and Human Services.
Information about NHGRI can be found at: www.genome.gov.
The National Institutes of Health (NIH) — The
Nation's Medical Research Agency — is comprised
of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services.
It is the primary Federal agency for conducting and
supporting basic, clinical, and translational medical
research, and investigates the causes, treatments,
and cures for both common and rare diseases. For more
information about NIH and its programs, visit http://www.nih.gov.